Pyrrolidyl-alkyl esters of parapropoxybenzoic acids



Patented July 29, 1952 PYRROLIDYL-ALKYL ESTERS OF PARA- PROPOXYBENZOIC ACIDS. L

William Bradley Reid, Jr., Kalamazoo, Mich., asv I signor to The Upjohn Company, Kalamazoo, Mich., a corporation of Michigan No Drawing. Application May 5, 1949,- Serial No. 91,624 I 11 Claims. 1

This invention relates to l-pyrrolidyl and l-(alkyl-pyrrolidyl) alkanol esters of a parapropoxybenzoic acid, and their acid addition salts.

The esters of this invention have the formula:

R-OQ-C o 00,112.11

wherein R is a member of the group consisting of normal and isopropyl radicals, R' is a member of the group consisting of pyrrolidyl-1 and loWer-alkyl-substituted pyrrolidyl-1 radicals, and n is an integer from 2 to 5, inclusive.

The esters of the invention are high boiling liquids which are readily soluble in most of the common organic solvents but insoluble in water.

The acid addition salts, such as the hydrochloride, hydrobromide, sulfate, nitrate, acetate,

tartrate, and citrate are generally crystalline solids with well defined melting points and are readily soluble in cold water, methanol, or

.ethanol, moderately soluble in isopropanol, ethyl RO-Q-C 01 with a pyrrolidylalkanol having the formula:

R'-CnH2n-OH.

wherein R, R and n have the values given previously. The corresponding acid bromides can also be used, if desired, although the method of preparing the compounds of this invention will be described with particular reference to the acid chlorides. The acid chlorides can be prepared readily and in excellent yield by treating the corresponding acid with thionyl chloride for a period of from one to several hours. The reaction can be conveniently carried out at the refluxing temperature of the mixture. An excess of thijonyl chloride is usually. employed and theexcess 2 subsequently removed by distillation under reduced pressure leaving the acid chloride as a residue which is generally sufliciently pure for use without further purification, but which can be fractionally distilled, to obtain greater purity, if desired. Acid bromides can be prepared in a similar manner using thionyl bromide.

The pyrrolidyl alkanols usedin preparing the esters of the present invention can be prepared conveniently inseveral ways. Thus, a suitable haloalkanol may be reacted with pyrrolidine or with an alkyl pyrrolidine and the desired alkanol obtained. In certain instances, it is advantageous .to first condense pyrrolidine or an alkyl pyrrolidine with a suitable halo-ketone, an ester of a suitable saturated halo-aliphatic acid, or an ester of a suitable alpha beta unsaturated aliphatic acid to form a pyrrolidyl ketone or an ester of a pyrrolidyl aliphatic acid. In other instances, it may be of advantage to condense a suitable amino alcohol with a succinic acid to form an N-hydroxy-alkyl succinimide or with a suitable gamma keto acid to form an N-hydroxyalkyl pyrrolidone. Theseketones or esters are then reacted with lithium aluminum hydride in absolute ether to produce the desired pyrrolidyl and lower-alkyl-substituted pyrrolidyl alkanols. Other pyrrolidyl alkanols may beyprepared by condensing a suitable pyrrolidine with formaldehyde and a suitable aliphaticaldehyde to give an N-pyrrolidylaldehyde which is readily'reduced with aluminum isopropoxide in isopropyl alcohol to the desired pyrrolidyl or alkylpyrrolidyl alkanol. I U 1 5 The reaction of an acid chloride and a pyrrolidyl alkanol can be conveniently carried out by mixing the two substances together in the presence of an inert diluent, such as dry xylene. Reaction usually occurs at ordinary temperatures and can be accelerated and carried substantially to completion by finally refluxing the mixture for about 30 minutes or longer. Upon'allowing the reaction mixture to cool,-the hydrochloride of the basic ester usually'crystallizes and can be separated from most of any inert diluent by filtering. The free ester can be recovered and purified by dissolving the crude hydrochloride in water, extracting the solution with ether, to remove any remaining inert diluent or other water insoluble substances, alkalizing the solution with sodium hydroxide, extracting with ether or other suitable organic liquid, and the extract eventual- 1y distilled to volatilize the solvent. The basic esters can be distilled under reduced pressure to obtain a higher degree of purity, if desired.

Acid addition salts of the basic ester, such as, the hydrochloride, hydrobromide, sulfate, phosphate, acetate, succinate, tartrate, benzoate, citrate, lactate, picrate, and other acid addition salts can be prepared readily by allowing the ester to react with the selected'acid in a solvent such as alcohol or a mixture of alcoholand ethyl acetate. salt remains as a residue which can be purified by recrystallization from alcohol, cr other suitable solvent. A mixture of ethyl alcoholjand ethyl acetate is particularly suitable in most instances. Acid addition salts ofLcertainjacids', especially the hydrochloride and citrate have well defined crystalline structures. Certain of the i polybasic acids, such as citric acid, combinewith the amino esters in equimolar proportions to form the monoamine salts. t r y The pyrrolidyl alkanols used in preparing the esters of the present inventioncan be a pyrrolidyhet apola p rol dylv ropan l a p rrolidylr -hlltanol, or a' pyrrolidyl-pentanol. The

can be either straighter branched. The pyrrolidine ringv can be jeith'erunsubstituted or it may is attached to thealkylene group through the nitrogen atom. Representative pyrrolidyl alkanols, which, among other's may be used in preparing esters of the invention. include:

2- (2 methylpyrrolidyl- -1) ethanol 2- (3 methyl'pyrrolidyl-l) -ethanol I 2- (2,3-dimethylpyrrolidyl-l) '-ethanol 2- (2,4 dirnethylpyrrolidyl l) '-ethanol 2-(2,5-dimethylpyrrolidyl-1) -'ethanol 2-(3,3-dirnethylpyrrolidyl 1} -.ethanol 2-(3,4-dirnethylpyrrolidyl5l) -ethanol 2-(2,4,4-trimethylpyrrolidyl-l) -ethanol 2-(2-ethylpyrrolidyl-lMethanol 2- (pyrrolidyl-l) -etha'n0l 3-(pyrrolidyl-1) propanol-li 2-methyl-2- (pyrrolidyl-l) -propanol-1 3- (Z-methylpyrrolidyl- 1) -propanol-l 2-methyl-3- (pyrrolidyl-l) -propanol-'1 2,2-dimethyl-3-(pyrrolidyl-l) -propanol-1 l-(pyrrolidyl-l)+propano1-2 1-(2,4edimethylpyrrolidyl-1)propan0l;2 1- (2,5-dimethylpyrrolidyl-1) -propanol-2 3- (pyrroli'dylel) -butan'ole1 4-(pyrrolidyl-1) -butanol-1 3-(pyrrolidyl-l).-butanol-2 1- (pyrrolidyl-l) -butanol-3 1- (pyrrolidyl-l) -pentano1- i 1- (3-butylpyrrolidyl-1) -propano1 2 2- 3-is0propylpyrrolidy1- 1) -ethanol 2- (3-pentylpyrrolidy1-1) -ethanol v 2- (2-methyl-3-pentylpyrrolidyl-1) -ethanol Although the. preferred method for preparing the compounds of the invention comprises reacting a para-propoxybenzoyl chloride with a pyrrolidyl-alkanol, it should be pointed out that they can also be prepared in other ways. which will be apparent to those skilled in the art. For ex- Upon distillation of the solvent, the.

ample, an alkali metal salt of a para-propoxybenzoic acid can be heated with a suitable pyrrolidyl-alkyl halide, preferably in a suitable solvent, such as ethanol, isopropanol, isopropyl ether, butanol et cetera and thedesired ester thereafter isolated from thereaction mixture.

Free basic esters within the'scope of the invention, include, among others:

7 benzoate 2- (3-methylpyrrolidyl-1) -ethyl para-isopropoxybenzoate;

'2 (2,3.dimethylpyrrolidyl-1) -ethyl para-n-propoxybenzoate 2 .(2A-dimethylpyrrolidyl-1) -ethyl para-n-propoxybenzoate 2'-(ZA-dimethylpyrrolidyl-1) -ethyl para-isopropoxyben'zoate 2 (3,3-dimethylpyrrolidyl-l) -ethyl para-n-proo ybcnzoate;

. 2- (3,3?dimethylpyrrolidybl) tits/1', para -isdpro- 'nu'm hydride in 25cm 2 (2-ethylpyrrolidyl-l) -ethyl para-n-propoxyb nzoa e 2-methyl-2- (pyrrolidyl-l) -l-propyl para-n-propoxybenzoate 2,2-dimethyl-3- (pyrrolidyl-l) -'1-propyl para-isopropoxybenzoate.

2,2 dimethyl3r. (DYrrolid'ylFl) 1propyl "para-npropoxybenzcate.

1 (2,4 dimethylpyrroli'dyll) z propyl para-npropoxybe'nz'oate. I

3-(pyrrolidyl-1) z-rsutyi para ir- 'prtpexybenzoate I 1- (pyrrol'iiiyl-l) 3431113371 "p'aia 'n' propfSXybenzo'ate l lpyrrolidyl ll pr'ityl "para i1 pro'pcxybe'nzoate v V .The following Preparations'rahd Examples are given to illustrate certain methods by which'some of the starting materials and compounds 'of'the pliabror'nopropionateiri'200"milliliters of benzene neg ams bi pyrr'olidine 'wasaldd'ed at a 's'ubStantially uniform rateover"aperiodfof'e5 rninutes.

The reaction was quite vigorousicausing the Solvent to boil. After allof thepyrrolidinejhad been added, the solution washeat'ed :iinder reflux for an hour, cooled, poured ihtojebp niiilli liters of ice-water, acidified with dilute aqueous hydrochloric acid and the two layers which resulted were separated. The aqueous'layer was washed with ether, made stroniily alkaline with cold aqueous sodium hydroxide, and extracted four times with 200-milliliter portions of ether. The ether extracts were combined, dried, the solvent removedand the. residue distilled at a reduced pressure of about lzimillimetersof mercuryabs'olute. There was thus obtained [56.7 grams (91.5 percent of the theoretical' yild) of ethyl'alplia- (pyrrolidyl-l) propionate, 'boil irigat' 84 degrees ce'ntigifade at apre's'su're of-12'iriil1imetersof mercury" absolute.

Preparation 2. 2- (pyrrolidyZ-I) -pr0mnol-1 To a solution of 7.6 'rergms fof lithium alumi- .tes ;urr'ene rw grams of ethyl alpha-'(p'yrrblidyl-l) profiiohate 10 2-13emethylpyrrolidyl-1) ethyl para-n-propoxywas added s1ow1yem eh t cause sentle eflu .ing of the ether. The mixture was then allowed to standior a-iew minutes without cooling and 20milli1iters ofwater added dropwise. The mixture was then cooled to about ten degrees centigrade by adding ice and acidified with aqueous hydrochloric acid. The aqueous layer was separated, washed with ether, and made strongly basic with concentrated sodium hydroxide. The basic solution'was then extracted repeatedly with ether, the ethereal extracts combined, dried with anhydrous potassium carbonate, .the ether. '.re-

moved, andthe residual oil iractionally. distilled.

There was thus. obtained,38.lr.grams"of .2-(pyrrolidyl-1)-propanol-1, boiling at .80 degrees cen- --tigr'ade at a. pressure of 11 millimeters of niercury absolute, and having an'indexof refraction,

41 of 1.4758. i 1

Preparation .3 Following substantially the procedure given in Preparations l and 2,"the'following alcohols were Preparation 4.3-(pyrrolidyZ-1 -propanoZ-1 A mixture was prepared consisting of 50.7

grams of sodium hydroxide, 45.7 grams of water, and 60.5 grams of pyrrolidine. Themixture was stirred vigorously and 100 grams of 3-chloropropanol-l added to the mixture at a rate such that the temperature of the mixture was maintained between about 75 and 100 degrees centigrade. When theaddition had-been completed, the mixture was stirred for an additional thirty minutes and allowed to stand for several hours. Suificient solid sodium hydroxide was then added to saturate the mixture and the oily layer which formed separated. The aqueous layer was extracted with benzene, the benzene extract added to the oily layer and the mixture fractionally distilled. There was 'thus obtained 65.5 grams of 3-(pyrrolidyl-l)-propanol-l, boiling at 115 degrees centigrade at a pressure of 43 millimeters of mercury absolute; and having an indexof res fraction, 11 of 1.4701.

Preparation 5.-4-(pyrroZidyl-1) -butanoZ-1- Following substantially thefprocedure givenin Preparation 4, 4-(pyrrolidyl-1)ebutanol-l was prepared, having a boiling point of 113 degrees centigrate at a pressure of 12 millimeters oi'mercury absolute; n =l.4705.; A I

Preparation 5 .-4- (pyrroZidyZ-i lmtanol-I panel-1 A mixture of 44.6 grams of 2- amino-2-methylpropanol-l, 108 grams of tetramethylene dibromide and 200 milliliters of toluene was boiled under reflux for three hours, 84- grams of sodium bicarbonate added and the boiling continued for an additional fifteen minutes. The mixture was then cooled to about 25 degrees centigrade, 3Q milliliters of aqueous; percent sodium hy droxide added, the organic layer which formed removed, suflicient water added to dissolve the salt and the aqueous solution extracted continuously with ether for nine hours. The ether extract and the organic layer were combined.

dried over anhydrous potassium carbonate and distilled. The distillate, melting at 27.5 degrees centigrade, was dissolved in dilute acid and treated with aqueous sodium nitrite to remove any "secondary amines. After extracting with ether, the aqueous solution was made basic with aqueous sodium hydroxide and extracted three times with -milliliter'portions of ether. The

etherextracts'were combined, dried, the ether removed and the residue distilled'at a reduced pressure of about l2 millimeters of mercury absolute. There wasthus obtained 54 grams (75.5 percent of the theoretical yield) of 2-methyl-2- (pyrrolidyl-l)'=propanol-l, boiling at 87 degrees 'centigrade at a pressure of 12 millimeters of mercury absolute and having. an index of refraction, 11,5 ,015 1.4720.

Preparation 7 .-2,2-dimet hyZ-3 (pyrroZidyl-I) propionaldehyde quarter. .After standing for three days. the mixture was made strongly basic with io percent sodium hydroxide and extracted five times with 100-milliliter portions of ether. The ether extracts were combined, dried over anhydrous potassium carbonate, the solvent removed. and the residue fractionally distilled at a reduced pressure of about 32 millimetersof mercury absolute. There was thus obtained 65.7 grams (42.3 percent of the theoretical yield) of 2,2-dimethyl-3-(pyr- 'rolidyl-l) -propionaldehyde, boilingv at 97 degrees centigrade at a pressure of 32 millimeters of mercury absolute, andhaving an index of refraction, n of 1.456.

Preparation 8.-2,2-dzmethyl-3- (pyrrolidyZ-l) propanoZ-l A mixture of 61.5 grams of 2,2-dimethyl-3-(pyrrolidyl-l) -propionaldehyde and 350 milliliters of isopropanol was removed from 40.8 grams of aluminum isopropoxide by slow distillation through a very efiicient column. After six hours of distillation, the distillate gave a negative test for acetone. The dark residue was cooled and 200 milliliters of 10 percent sodium hydroxide added. The organic layer was separated from the aqueous layer, and saturatedwith aqueous potassium carbonate to form. two layers. The aqueous fraction wasfseparated, combined with the aqueous layer obtained previously and extracted six times with 100-milliliter portions oi ether. The ether extracts were combined and dried over anhydrous potassium carbonate. The ether was removed and the residue fractionally distilled at a reduced pressure of about 26 millimeters of mercury absolute. There was thus obtained 25.6 grams (41.7 percent of the theoretical yield) of 2,2 dimethyl 3 7 (pyrrolidyl-1)-propanol-l, boiling at 111 degreescentigrade at a pressure of 26 millimeters of: mercury absolute, d avin e x of, r t a ti nm i o 4 9..

-' Preparation e, 9 -1 pg rol idyl-i pentancne-4 solution of grains of 2- tpyrrolidyl-l) ethyl .ichlori de in 100. milliliters of benzene was added dropwise toasuspensionofthe sodium V H I V l v fiuX-for seventeen hours, cooled to. about l'2j0 .:de'g}r es. centigrade, 430 milliliters-f cold'. thirty percent, sodium hydroxide solution added, andthe.resulting oilyorganic layer was separated. Theaqueou's ,layer was extracted three times with 100-milIilit'er-portions of benzene. The organic layer and th'ebenzen'e extracts were combined, dried, the benzeneremoved, and the residueidistilled at a; reduced pressure of about 12 millimeters of mercury absolute. There was thus obtained 129 grams of 1-(pyrrolidyl-1)- pentanone-4, distilling at 92-98 degrees centigrade at a pressure of 11-13 millimeters of mercury absolute. Redistillation gave 98.2 grams of 1-'j(pyrrolidyl-D-pentanone-4; 12 of 1.4589, distilling at 93-95 degrees centigrade at a pressure of. 11 millimeters of mercuryabsolute.

Preparation'10.-1-- (pyrroZz'dyZ-Z) -pentanol- 4;

Preparation 11.1-'(2-hi/droa:yethyZ) -5-methyl- ,pyrroZz'done-Z A suspension of 0.2'gram of platinum oxide catalyst in 25'milliliters of absolute ethanol was reduced to platinum, a solution of 34.8 grams of levulinicacid and 37.8 grams of ethanolaminein 75 milliliters ofabsolute alcohol added, and the mixture hydrogenated, at about 50 poundspressureand roomtemperature for about four hours, at which time the theoretical amount of hydrogen had-been absorbed. After the catalyst and solvent had been removed the residue wasfractionally distilled; There "was thus, obtained 425 grams (100 percent of the theoreticalyield) of 1-(2-hydroxyethyl) -5methyl pyrrolidone, boiling at 167 degrees centigrade at a pressure of, 12 millimeters ofmercury absolute and having an index of refraction, n of 114900.

Preparation 12.-2 (2,-.meth: /Z1 yrroZicZyZ- -1) ethanol an index of re- "milliliters of ether. Distillation gave-35 grams (76* percent of the theorectical yield) of- 2-(2- me'thyl-pyrrolidyl-l)--ethanol, boiling at 87 degrees centigrade at a pressure oflfi-millimeters or-mercury absolute, and'having an index of retraction- 11 of 1.4680. I Preparation]v 1 3 .By .a. procedure. similar. to: that: described in Preparations-111 and1'2, the following compounds wer'e:.pr'.epared.:v

1.1.2 (2,3!dimethylpyrrolidyl-l) -ethanol,. boilme at .86; degreesscentigradei at; a pressure of. 13 millimeters of mercuryl absolute, .index of refracti'on,*1n of 1.4661;

2.:3 (2emethylpyrrolidyb1)'-propanole1,. boilingatlOO degreeslcentigrade at-a pressure of 18 millimeters of mercury absolute, index oirefraction, 12 of 1.4672.

Preparation .14. N.-(Z-haarQxyerhz/Z).-alphamethylsuccin'imide A mixture of 66 grams of alpha-methyl-succini'c acid; and ,.73.4.,grams 10fmonoethanolamine was heate by: means; of "an; oil bath, the temperature. 01: the mixture. gradually rising to 260 degrees centigrade, ,u ntildistillation ceased. The residue was distilled: under a. reduced pressure of about; oneemillimeter of mercury; absolute to obtain; a viscous, oil, which, upon fractional distillation, yielded-v 67.81egrams (86.4 percent of the theoretical yield) .ofgN-,( ,hydroxyethyl) -alphamethyl-succinimide, ,boiling at 102 degrees centigrade at'a pressure 0f..0,.-01 millimeter of mercury absolute, and'having' an index ofrefraction, n of 1.4970.

Preparation 1 5 .-2- (3-methylpyrrolidyl) ethanol- By; a procedure similar to that described in Preparation 2, 62.8 grams of N-(2-hydroxyethyl) -alpha-methylsuccinimide was reduced with-30 grams of lithium aluminum hydride. .Upon fractional distillation, therewas obtained 35 grams (68.1*percent of thetheoretical yield) .of 2-(3-methylpyrrolidyl)-ethanol, boiling at 86 degrees. centigrade at a pressure of 16 millimeters ofzmercuryabsolute, and .havingra-refractiyeyindex, 15 4.5, .of;1-.46.80.'

Preparation 16 were, prepared:.

'1. 2-(3,3rdimethylpyrrolidyle1) -e thanol, boiling .at 31 degrees. centigrade at a pressure of. 13 millimeters of mercury absolute,indexofurefraction, n of 1.4580.

2;. 2e(1%;4-dimethylpyrrolidyl-1') -ethanol, boiling at,86 degrees centigrade at a pressureof 12 millimeters'of merciiryabsolute, index of refraction, -nb% .1.0f" 1.45.94; v

'3; 525 (2,4,4 -.trimethylpyrrolidyl- 1) ethanol, boiling at 84degrees centigrade at a pressure of 14 millimeters of 'mercury absolute, index of refraction, n 5,-of 1.4535.

Preparation 17,-ptara-n-Propoacybeneoyl chloride A" solution: of 6761 grams of para-n-propoxybenzoic--acid and-808 grams-of thionyl chloride in oneliterotbenzene was-boiled underreflux for four-hours, concentrated to remove substantially all =of-theexcess thionyl chloride and ben- 26116; and the residue distilled at a reduced pressure of about 12 millimetersof mercury --absolute. There was thus obtained 610.7 grams (82 percent of the theoretical yield) of .para-npropoxybenzoyl chloride, boiling at 149-151 degrees centigrade ata. pressure of 12 millimeters of'mercuryv absolute.. f

Preparation '1 8.' -'para-Isopropo:ryb enzoyl chloride P Following substantially the procedure given in Preparation 17, 399.2 grams (88.5 percent of the theoretical yield) of para-isopropoxybenzoyl chloride, boiling at 149-151 degrees centigrade at a pressure of 15 millimeters of mercury absolute, was obtained from 397.3 grams of para-isopropoxy-benzoic acid.

Example J.-.-3(pyrrolidyl-1)-1-propyl para- V isoproporcybenzoate I .A;-solution of 18.3; grams of para-isopropoxybenzoyl chloride in 25 milliliters of dry benzene was added at a substantially uniform rate to a boiling solution of 12.9 grams of 3-(pyrro1idyl-1) propanol-l in '125 milliliters of benzene. Boiling under reflux was continued for six hours, the mixture was cooled to about 30 degrees centigrade, .100 milliliters of water added and the layers thus formed separated. The aqueous layer was made basic with dilute aqueous sodium hydroxide and extracted'three times with 50-milliliter portions of ether. The ether extracts were combined, dried, concentrated to about '50 millilitersjand the .residuedistilled' at a reduced pressure of about. oneinillimeter of mercury absolute. There was thus obtained 21.9 grams of 2- (pyrrolidyl-l) -1-proply para isopropoxybenzoate, boiling at 161-162 degrees centigrade at a pressure of 0.03 millimeter of mercury absolute, and having anindex of refraction, 17. 5 01': 1.5257. Analysis: 1

Calculated for C11H2sO2N: .N, 4.80 Found: 5.00

Example 2.'2 mlrro'lidyl 1) 1 propyl paraz'sopropoxybenzoate hydrochloride Analysis:

Calculated for C17H26O3NC1I Cl, 10.8 Found: 10.6

m a, 39-21-12 eth zpy'r'mzcz z 1) ethyl A solution of 18.3 grams of para-n-propoxybenzoyl chloride in 25 milliliters of benzene was added at a substantially uniform rate over a period of 30 minutes to a refluxing solution of 18.3 grams of 2-(2-methylpyrrolidyl-l) -ethanol. Boiling under reflux was continued for two and one-half hours, the mixture cooled to about 30 degrees centigrade, fifty milliliters of water added and the. layers so-obtained separated. The aqueous layer was made alkaline with dilute aqueous sodium hydroxide and extracted three times with 50-milliliter portions of ether. The ether extracts were "combined, dried, concentratedto' about 30 milliliters. and the residue distilled under a reduced pressure ofabout one 10 millimeter of mercury absolute. There was thus obtained 23.4 grams (84.1 percent of the theoretical yield) of 2-(2-methyl-pyrrolidyl-1) -ethyl para-n-propoxybenzoate, boiling at 138-139 de grees centigrade at a pressure of 0.03 millimeter of mercury absolute, and havingan index of Analysis: I 1

Calculated for C17H2603NC1Z Cl, 1 0.8 Found: 10.8

. m ffi Following substantially the procedure given in Examples 1 and 2, the following esters and their hydrochlorides were prepared:

1. 2 (3 methylpyrrolidyl 1) -ethyl para-isopropoxybenzoate, boiling at 143-144 degrees centigrade at a pressure of 0.05millimeterof mercury absolute.

Analysis:

Calculated for 017112503: Found: 4.83

The hydrochloride, melted at 111-112 degrees centigrade. Analysis: l.

Calculated for C'rzH sOaNCh Cl, 10.8 Found: 10.7 1,

2. 2-(2-methylpyrrolidyl-1) -ethyl para-n-propoxybenzoate, boiling at 141-142 degrees centigrade. at a. pressure of 0.05 millimeter of mercury absolute. 1

Analysis: h Calculated for C17H25O32 15114.80; Found: 4.96 if r The hydrochloride melted at 114-116 degrees centigrade. v c. I

Analysisz' 3 fl I Calculated for CrzI-IzsOsNCl: Cl, 10.8

Found: 10.7.

3. 2-(2-methylpyrrolidyl-1) -ethyl .para iso propoxybenzoata boiling at 168-172 degrees centigrade at a pressure of 0.3 millimeter of mercury absolute.

Analysis: I I I Calculated for C'1'7H25O3N2 N, 4.80 Found: 4.80 I

The hydrochloride ,melted at 163 .5-1 64.5 degrees centigrade. I w 7 Analysis: 1'

Calculated for C17H26O3NC11.C1, 10.8 .1

Found: 10.8

4. 2-(3,3-dimethylpyrro1idyl-1)-ethyl para-npropoxybenzoate, boiling at 146 degrees centi:

grade at a pressure of :04 millimeter of mercury absolute. 1 i

Analysis: r

Calculated fQrCmHzwOsN: 17.4.53

Found: 4.69 f

The hydrochloride meltedjjat 151-152 degrees centigrade.

Analysis: 0

Calculated for CmI-IzaNOcCl! C1,;10.4 Found: 10.2 V

5. 2- (3,3-dimethylpyrro1idylr1) -ethyl para-isopropoxybenzoata, ,boiling at 141-142 degrees centigrade at a pressure of 0.04 millimeter of mercury absolute.

Analysis: 7 I v a v Calculated ferCraHzqNOa: N, 4.58 Found: 4.61 Y The hydrochloride melted at 155-156 degrees centigrade.-

Analysis:

Calculated for CmHzsNOsClZ C1, 104 Found: 10.3

Analysis: Calculated for QiBI-I2'1NO31N, 4.58 Found: 4.57

The hydrochloride melted at 106-108 degrees centigrade.

Analysis Calculated for C18H28NO3C12 Found: 10.1

8. 2- (pyrrolidyl-l) -1-propyl para-n-propoxy- 'benzoate, boiling at 152-153 degrees centigrade at a pressure of 0.25 millimeter of mercury absolute.

Analysis:

Calculated for CnHzsNOa: Found: 4.72

The hydrochloride centigrade.

melted at 120-121 degrees Analysis: I

Calculated for C17H25NQ3C1: CI, 10.8 Found: 10.7

9. 2- (pyrrolidyl-1)-1-propyl para-isopropoxybenzoate, boiling at 151-152 degrees centigrade at a pressure of 0.2 millimeter of mercury absolute.

Analysis:

Calculated for C17I-I25NO32 N, 4.80 Found: 4.91

- The citrate'melted at 109.5-1105 degrees centigrade;

Analysis: f

Calculated for CzaHzaNOrn: N, 2.90

Found: 2.93

10. 1- (pyrrolidyl-l) -2-'propyl para-n -propoxybenzoate, boiling at 127-130 'degrees centigrade at a pressure of 0.03 millimeter of mercury absolute.

Analysis:

Calculated for C17H25NOGZ N, 4.80 Found: 4.74

The hydrochloride melted at 150-152 degrees centigrade.

Analysis:

Calculated for Found: 10.6

11. 1- (pyrroliclyl-l) -2 -propyl para-isopropoxybenzoate, boiling at 1525-1535 degrees centigrade at a pressure of 0.15'mfl1iineter of mercury absolute.

Analysis:

Calculated for CrzI-l'asNOs: N, 4.80 Found: 4.77

The hydrochloride melted at 147-148 degrees centigrade.

Analysis: l V

Calculated for .ci'lHztNOsCl: Cl, 108 Found: 10.6 V v 12. 3-'(pyrrolidyl-1) -2'-butyl para-n-propoxybenzoate, boiling at -136 degrees centigrade. at a'pressure of 0:04 millimeter of mercury absolute.

-Analysis: I

Calculated for .CmHzvNOa: N. .458

Found:.4.55

The hydrochloride melted at 101-1031 degrees centigrade.

Analysis: H

Calculated for CmI-IzaNOaCl: C1, 10.4. Found: 102 I v v 13. 3- (pyrrolidyl-l) -2-butyl para-isopropoxybenzoate, boiling at 128-129 degrees centigrade at a pressure of 0.03 millimeter of mercury absolute. 1 v

Analysis: l v

Calculated for CmHz'zNOa: N, 4.58

Found: 4.58 l 1 The hydrochloride meltedat 153-154 degrees centigrade. r

Analysis:

Calculated for CraHzsNOsCl: C1,.

Found: 10.1

14. 2-methyl-2-(pyrrolidyl-l)1-propyl paran-propoxybenzoate, boiling at 132 degrees centigrade at a. pressure absolute.

Analysis: Calculated for CmHzvNOa: N, 4.58 Found: 4.61- a v The hydrochloride melted'at 133-134'degrees centigrade.

Analysis:

Calculated for Found: 10.3

15. 2-methyl-2-(pyrrolidyl-l)-1-propyl paraisopropoxybenzoate, boiling at 176-178 degrees centigrade at a pressure of 0.9 millimeter of mercury absolute.

of 0.05 millimeter of mercury mammal; 01. 10.4

13 Analysis:

Calculated for CmI-IzvNOa:

Found: 4.05

The hydrochloride melted at 156-1565 degrees centigrade.

Analysis: 7

Calculated for CraHzaNQsCl: Cl, 10.4 Found: 10.2

16. 3-(pyrrolidyl-1) -1-propy1 para-n-propoxybenzoate, boiling at 132-134 degrees centigrade at a pressure of 0.03 millimeter of mercury absolute.

Analysis:

Calculated for C1'1Hz5NO3Z N, 4.80 Found: 4.89

The hydrochloride melted at 126-1265 degrees centigrade.

Analysis:

Calculated for CrzHzwNOaClt Cl, 4.27 Found: 4.43

17. 3-(pyrrolidyl-1)-1-butyl para-n-propoxybenzoate, boiling at 146-147 degrees centigrade at a pressure of 0.03 millimeter of mercuryabsolute. I

Analysis:

Calculated for CrzHz'zNOst Found: 4.61

The hydrochloride melted at 84-85 degrees centigrade.

Analysis:

Calculated for CraI-IzsNOaCl: Cl, 10.4 Found: 10.3

18. 3-(pyrrolidyl-1) -1-butyl para-isopropoxybenzoate, boiling at 122-123 degrees centigrade at a pressure of 0.04 millimeter of mercury absolute.

Analysis:

Calculated for CrsHzwNOa: N, 4.58 Found: 4.80

The hydrochloride melted at 106-107 degrees centigrade.

Analysis:

Calculated for CmI-IzsNOsCl: Cl, 10.04 Found: 10.2

19. 2-methyl-3-(pyrrolidyl-l) -1-propyl paran-propoxybenzoate, boiling at 170-171 degrees centigrade at a pressure of 0.75 millimeter of mercury absolute.

Analysis:

Calculated for Ciel-127N031 N, 4.58 Found: 4.57

The hydrochloride melted at 147-148 degrees centigrade.

Analysis:

Calculated for CiaHzaNOsCl: Cl, 10.4 Found: 9.9

20. 2-methyl-3-(pyrrolidyl-1) -1-propyl paraisopropoxybenzoate, boiling at 132-133 degrees centigrade at a pressure of 0.04 millimeter of mercury absolute.

Analysis:

Calculated for C1aH2'lNO32 N, 4.58 Found: 4.64

The hydrochloride melted at 177.5-1785 degrees centigrade.

Calculated for C18H27NO3: N,-4.58 Found:

The hydroch oride 'melted at; 153-154 degrees centigrade.

' Analysis:

Calculated for chrhmoeclz 01, 10.4 Found: 10.3

22. 3 (2 methylpyrrolidyl-l) -1, -propyl paraisopropoxybenzoate, boiling at 148-1485 degrees centigrade at a pressure of 0.04-millimeter of mercury absolute.

Analysis:

Calculated for CiaHMNOsZ N, 4.58

Found:

The hydrochloridecentigrade.

Analysis: 7

Calculated for CmHzaNQaCl: Cl, 10.4 Found: 10.2

23. 4-(pyrrolidyl-1)-1-buty1 para-n-propoxybenzoate (undistillable) Analysis:

Calculated for CisHz'zNos: N, 4.58 Found: 4.29

The hydrochloride melted at -112 degrees centigrade.

Analysis:

Calculated for CraHzaNoaCl: C1, 10.4 I Found: 10.2

24. 4-(pyrrolidyl-1) -1-butyl para-isopropoxybenzoate.

Analysis:

Calculated for CmHz'zNOst N, 4.53 Found: 4.17

The hydrochloride melted at -121 degrees centigrade.

Analysis:

Calculated for CiaHzsNOsCl: Cl, 10.4 Found: 10.4

Various modifications may be made in the compounds of the present invention without departing from the spirit or scope thereof, and it is to be understood that I limit myself only as defined in the appended claims.

I claim:

1. A member of the group consisting of (a) esters having the formula:

ROG-GOOGHMR wherein R is a member of the group consisting of the n-propyl and isopropyl radicals, R is a member of the group consisting of pyrrolidyl-l and lower-alkyl-substituted pyrrolidyl-l radicals and n is an integer of the group consisting of 2, 3, 4, and 5, and (5) acid addition salts thereof.

melted at .132-1 33ddes rees' 15 2. Acid addition salts of esters having-the formula: j

Wh'erein R is n pi'opyhn'is 'the integen 2, and R is a iower-alkyl-substituted pyrroiidyl-l' radical. 3. Acid addition salts of esters having the formula:

R- CQ CO o 0.11MB

wherein R is nepropyl, n is theinteger 2 ,.andR' is a methyl-substituted pyrrolidyl-l radical.

4. Acid addition salts of esters having the formula:

wherein R is isopropyl, n is the integer 4, arid R is pyrrolidyl-l. k y ,7 V

6.'Acid addition" salts of esters having the formula:

i6 wherein R. is n-propyl, nis the integer 4, and R is pyrrolidyl-l. r

7. 3-(pyrrolidyl-1) -propyl para-npropoxybenzoate hydrochloride. v

8. 2-(3-methylpyrrolidyl-l)-ethyl para-n-propoxybenzoate hydrochloride.

9. 2-(pyrrolidy1-1) -1-propyl para-n-propoxy benzoate hydrochloride.

10. 3-(pyrro1idy1-1) -2-buty1 para-isopropoxybenzoate hydrochloride. 1 v

11. 2-methy1-3-(pyrrolidyl-l)-1-propy1 n-propoxybenzoate hydrochloride.

WILLIAM BRADLEY REID, JR."

para- REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Rohmann May '25, 1937 OTHER REFERENCES Number (March 1931) pp. 1015-1025;. v I

Moore: Jour. Amer. Pharmaceutical Assn, v01.

33 (July 1944), Scientific Edn., pp. 193-204. 

1. A MEMBER OF THE GROUP CONSISTING OF (A) ESTERS HAVING THE FORMULA: 